Residual insulin secretion and management of type 1 diabetes: Interest of new C-peptide assays.

peer reviewedPlasma C-peptide represents a direct measure of endogenous insulin secretion. The development of new assays for measuring C-peptide have made it possible to demonstrate that a low insulin secretion persists in 30 to 80% of subjects with type 1 diabetes (T1D), even among those with long-standing disease. Several studies have established that the persistence of B cell function of the islets of Langerhans is associated with a protection against the development of microvascular complications and resulted in a significant reduction in the prevalence of severe hypoglycaemia in people with T1D. Further studies are needed to clarify the underlying pathophysiological mechanisms and the therapeutic strategies that would maintain B-cell function and thus improve the quality of life of patients with T1D.Le peptide-C plasmatique constitue une mesure directe de la sécrétion endogène d’insuline. Le développement de nouveaux dosages du peptide-C a permis de démontrer qu’il persiste chez 30 à 80 % des sujets diabétiques de type 1 (DT1) une faible sécrétion d’insuline, même sur le long terme. Plusieurs études ont établi que la persistance de la fonction B des îlots de Langerhans était associée à une protection contre le développement des complications microvasculaires et engendrait une réduction significative de la prévalence des hypoglycémies sévères chez les personnes DT1. Mais des études complémentaires sont encore nécessaires afin de préciser les mécanismes physiopathologiques sous-jacents et les stratégies thérapeutiques qui permettraient de maintenir la fonction de la cellule B et d’améliorer ainsi la qualité de vie des sujets avec un DT1

Alcohol policy changes and 22-year trends in individual alcohol consumption in a Swiss adult population: a 1993-2014 cross-sectional population-based study.

Evidence on the impact of legislative changes on individual alcohol consumption is limited. Using an observational study design, we assessed trends in individual alcohol consumption of a Swiss adult population following the public policy changes that took place between 1993 and 2014, while considering individual characteristics and secular trends. Cross-sectional study. Swiss general adult population. Data from 18 963 participants were collected between 1993 and 2014 (aged 18-75 years). We used data from the 'Bus Santé' study, an annual health survey conducted in random samples of the adult population in the State of Geneva, Switzerland. Individual alcohol intake was assessed using a validated food frequency questionnaire. Individual characteristics including education were self-reported. 7 policy changes (6 about alcohol and 1 about tobacco) that occurred between 1993 and 2014 defined 6 different periods. We predicted alcohol intake using quantile regression with multivariate analysis for each period adjusting for participants' characteristics and tested significance periods. Sensitivity analysis was performed including drinkers only, the 10th centile of highest drinkers and smoker's status. Between 1993 and 2014, participants' individual alcohol intake decreased from 7.1 to 5.4 g/day (24% reduction, p<0.001). Men decreased their alcohol intake by 34% compared with 22% for women (p<0.001). The decrease in alcohol intake remained significant when considering drinkers only (28% decrease, p<0.001) and the 10th centile highest drinkers (24% decrease, p<0.001). Consumption of all alcoholic beverages decreased between 1993 and 2014 except for the moderate consumption of beer, which increased. After adjustment for participants' characteristics and secular trends, no independent association between alcohol legislative changes and individual alcohol intake was found. Between 1993 and 2014, alcohol consumption decreased in the Swiss adult population independently of policy changes

Ret is essential to mediate GDNF’s neuroprotective and neuroregenerative effect in a Parkinson disease mouse model

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival and regeneration-promoting factor for dopaminergic neurons in cell and animal models of Parkinson disease (PD). GDNF is currently tested in clinical trials on PD patients with so far inconclusive results. The receptor tyrosine kinase Ret is the canonical GDNF receptor, but several alternative GDNF receptors have been proposed, raising the question of which signaling receptor mediates here the beneficial GDNF effects. To address this question we overexpressed GDNF in the striatum of mice deficient for Ret in dopaminergic neurons and subsequently challenged these mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Strikingly, in this established PD mouse model, the absence of Ret completely abolished GDNF’s neuroprotective and regenerative effect on the midbrain dopaminergic system. This establishes Ret signaling as absolutely required for GDNF’s effects to prevent and compensate dopaminergic system degeneration and suggests Ret activation as the primary target of GDNF therapy in PD